All, Would anyone be willing to comment on the applicability, or lack thereof, of applying the various literature referenced techniques to PD/biomarker data, including differences in assumptions and practical considerations? Thank you, Mark
Mark C. Peterson Amgen Inc. One Amgen Center Drive MS 28-3-B Thousand Oaks, CA 91320 ________________________________ From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] On Behalf Of [EMAIL PROTECTED] Sent: Saturday, May 24, 2008 4:58 PM To: [EMAIL PROTECTED] Cc: [email protected] Subject: RE: [NMusers] Visual predictive check! Ken and All, The recent paper on JPP "Impact on censoring data below an arbitrary quantification limit on structural model misspecification" 2008, 35:101-16, by Byron, Fletcher and Brundage is still fully available on line and it speaks volumes about bioanalytical motivated LLOQ and pharmacokinetics modeling. Just for those who haven't read it, I vividly reccomend so. Cheers --------------------------------------------------------------- Luis M. Pereira, Ph.D. Assistant Professor, Pharmacometrics Massachusetts College of Pharmacy and Health Sciences Childrens Hospital Boston / Harvard Medical School 179 Longwood Ave, Boston, MA 02115 Phone: (617) 732-2905 Fax: (617) 732-2228 ________________________________ From: [EMAIL PROTECTED] on behalf of Ken Kowalski Sent: Fri 5/23/2008 11:22 AM To: 'Nick Holford'; [email protected] Subject: RE: [NMusers] Visual predictive check! Nick, Yes, I'm making the assumption that a measured concentration cannot be negative. Educate me about chemical assays. Can you get troughs rather than peaks in a chromatogram such that the area below zero is integrated and reported as a negative concentration? If so, what would happen if you assayed a bunch of pre-dose samples (before drug is administered) where the true mean concentration is zero? Would we get measured concentrations symmetrically distributed about zero (with about 50% of the measured concentrations reported as negative and 50% positive)? If so, then a normal residual error model may indeed be appropriate. Ken
